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The Primary Care of Women With Chronic Renal Disease
The Primary Care of Women With Chronic Renal Disease Andrea J. Singer Nephrologists are often responsible for the primary care of their female patients with chronic renal disease. As such, they must be cognizant of medical issues that are unique to women. Awareness and implementation of routine health care maintenance and cancer screening recommendations are essential. The provision of reproductive health services, which includes menstrual history assessment, contraception counseling, and services relating to child bearing and sexual functioning, is also necessary. Menopausal health concerns and hormone replacement therapy are frequently overlooked and need to be addressed. In general, the primary care of women with chronic renal disease is similar to that of women without renal disease and should adhere to current standards of preventive care. © 2000 by the National Kidney Foundation, Inc. Index Words: End-stage renal disease; preventive care; reproductive health; menopause.
he population of women with chronic renal disease, including patients with endstage renal disease (ESRD) on peritoneal dialysis and hemodialysis, grows each year. Nephrologists provide most of the medical care to this patient population. Although nephrologists generally address medical issues related to renal disease and the comorbid conditions which frequently exist, attention must be given to preventive care and routine health care maintenance. The need for preventive care in women with ESRD is no less than that for the female population at large. Nephrologists must be prepared to address issues concerning screening for cancer, menstruation, birth control methods, childbearing, and menopause.
T
Prevention and Screening One of the main roles of the primary care physician is to help women stay healthy. If disease does occur, it must be diagnosed as early as possible so as to afford the greatest likelihood of cure or long-term control of the problem, thereby reducing the risk of significant secondary morbidity. The screening and
From the Departments of Medicine and Obstetrics/ Gynecology, Georgetown University Medical Center, Washington, DC. Address correspondence to Andrea J. Singer, MD, Georgetown University Medical Center, Departments of Medicine and Obstetrics/Gynecology, 3 PHC, 3800 Reservoir Road, NW, Washington, DC 20007; e-mail: singeraj@gusun. georgetown.edu. © 2000 by the National Kidney Foundation, Inc. 1073-4449/00/0703-0003$3.00/0 doi:10.1053/jarr.2000.8127
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prevention strategies most important for any given woman will depend on her individual risk profile. The strategies will also change as the woman ages, and they will evolve through the phases of her life. With a few exceptions, screening recommendations for the woman with ESRD are no different than those for the average woman. This section will cover a series of strategies that can be used in practice to optimize the patient's well-being. Routine Assessments Periodic health assessments provide an excellent opportunity to counsel patients about preventive care. These assessments, annually or in an ongoing manner with the ESRD patient, should include screening, evaluation, and counseling based on age and risk factors (Table 1). Personal behavioral characteristics are important aspects of a woman's health. Cigarette smoking contributes substantially to morbidity and mortality. Therefore, the primary care of women should include a routine assessment of smoking status, strong and repeated advice to all smokers to quit, and assistance for those smokers who are ready to stop. Alcohol and drug use are also serious and common problems for women in the United States, and physicians can play a role in decreasing women's risk. All physicians, but especially those providing primary care, must be alert to signs of substance use and abuse, must ask direct questions, and must be willing and able to counsel their patients or refer them for help when necessary. Using the standard weight/height charts or
Advances in Renal Replacement Therapy, Vol 7, No 3 (July), 2000: pp 202-209
The Primary Care of Women With ESRD
Table 1. Preventive Health Services in Adults
Preventive Service Counseling Tobacco/ alcohol! drugs Nutrition Exercise Sexual practices SeU-breastexarnination Sun exposure Injury prevention (seatbelts/hehnets/
Frequency Annually Annually Annually Annually Annually Annually Annually
guns)
Physical examination Blood pressure Weight Height Clinical breast examination Laboratory tests and procedures Cholesterol Pap smear
Manunography Stool for occult blood Flexible sigmoidoscopy
Minimum of every 2 years Each visit or annually Annually Annually after age 40
Every 5 years Begin at age 18 or at the onset of sexual activity; annually for 3 years; if normal, screening interval can be extended to every 2 to 3 years at discretion of physician and patient Every 1 to 2 years from age 40-49; annually after age 50 Annually after age 50 Every 3 to 5 years after age 50
Adapted and reprinted from u.s. Preventive Services Task Force: Guide to Clinical Preventive Services (ed 2). Baltimore, MD, Williams & Wilkins, 1996.13
calculations of body-mass index, by middle age, approximately 35% of white women and 60% of black women are overweight or obese. Proper dietary and exercise habits can substantially reduce the risk of obesity and the illnesses and disabilities associated with it. Decreasing the number of calories from fat, increasing fiber content, maintaining dietary balance in the context of an appropriate renal diet, and identifying a fitness program that will fit a woman's lifestyle and in which she will participate regularly are all important issues for the primary care physician and patient to discuss.
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Just as weight and blood pressure are followed closely in the patient with chronic renal disease, height should be followed as well. It should be measured on initial examination, and thereafter, on a yearly basis. Decreases in height of more than one-half inch should raise concern and alert the physician to the possibility of bone density loss and/or osteoporotic vertebral fractures. Cancer Screening Breast cancer is the most common cancer in women in the United States. Mammography may be used as a screening device or as an adjunct in the diagnosis of a palpable breast mass. At the present time, mammography is the only screening method widely available to detect subclinical or occult breast cancer. Largescale, prospective, controlled studies of screening for breast cancer show that mammography reduces the breast cancer mortality rate for women over 50 years of age. The data for screening mammography in women less than 50 years of age is equivocal and currently limited. Therefore, it is recommended that mammography be offered every 1 to 2 years in women age 40-49 and annually to women over age 50. In addition to mammography, clinical breast examination should be performed annually. For high-risk women (such as those with a family history of premenopausal breast cancer in a first-degree relative or genetic susceptibility documented by the presence of BRCA-l or BRCA-2), screening should begin earlier. Women should be screened for cervical cancer and its precursors. Routine Pap smear screening will decrease the incidence and mortality rates of cervical cancer. The current recommendations for when to perform this test generally adhere to guidelines established by the American College of Obstetricians and Gynecologists and the United States Preventive Health Task Force. Routine Pap tests are recommended annually for women age 18 to 65 until 3 consecutive normal results are obtained, and thereafter at the discretion of the physician and patient. Whether it is cost effective to extend screening beyond age 65 is not entirely apparent. Because many patients in the over-65 age group have not been screened or have not been screened regularly, it seems prudent to allow the physician to make recom-
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mendations for the individual in this age group. Colon cancer causes more deaths among women than all gynecologic malignancies combined. In most cases it is preceded by an adenomatous polyp or polyps. Both polyps and early colonic cancer can be detected by routine screening. The digital rectal examination has limited usefulness because less than 10% of colorectal cancers are within reach of the examiner's finger; however, it can easily be performed at the time of pelvic examination in women. Testing of stool for occult blood is limited in sensitivity and specificity, but it can aid in early detection. Although controversy as to the efficacy of screening in the general population and the best methods for screening exists, the American Cancer Society recommends digital rectal examination beginning at age 40, testing of stool for occult blood annually beginning at age 50, and sigmoidoscopy every 3 to 5 years beginning at age 50. The American College of Physicians supports the American Cancer Society in regard to stool for occult blood and sigmoidoscopy. More comprehensive assessments, such as colonoscopy or double air contrast barium enema, should be undertaken if warranted by other risk factors. The skin is the largest human organ and has the highest exposure to direct carcinogens, particularly sunlight. It is not surprising, then, that squamous cell and basal cell carcinomas are 2 of the most common forms of cancer. Though squamous and basal cell cancers are not usually associated with major disability or death, malignant melanoma is associated with increased mortality if not diagnosed early. During history taking, the physician should inquire as to whether a new skin growth has appeared or an existing one has changed color or become symptomatic. An annual complete skin examination should be performed with special attention given to sun-exposed parts of the body. Patients in high-risk groups, such as those with increased recreational or occupational exposure to sunlight, may be referred to a dermatologist. Instruction in skin selfexamination, including vulvar skin, should be a routine part of wellness care. Recommendations for the use of protective clothing, hats, and sunscreen with a sun protective factor (SPF) of 15 or greater should be made as well.
Immunizations General recommendations on immunization in the United States are those of the Immunization Practices Advisory Committee of the Center for Disease Control. Six vaccines are recommended for routine use in adults living in the United States. These include tetanus-diphtheria, measles, rubella, influenza, hepatitis B, and pneumococcus (Table 2). Several points should be highlighted with respect to immunizations in women with chronic renal disease. Influenza vaccines are recommended annually, regardless of age, for all people with renal dysfunction. Pneumococcal vaccine is similarly recommended, regardless of age, for patients with chronic renal failure. Though generally given as a 1-time dose, pneumococcal revaccination is recommended 5 years after the initial vaccination for people at the highest risk of fatal pneumococcal infection or rapid antibody loss, such as those patients with chronic renal disease. The hepatitis B vaccine series should be administered to patients in hemodialysis units and patients with renal disease that may result in dialysis. For dosing regimens, please refer to Table 2.
Reproductive Health Reproductive health encompasses a broad range of services for women of reproductive age, including contraception; sexually transmitted disease and HIV prevention; prenatal, intrapartum, and postpartum care; and counseling regarding healthy lifestyles and the benefits of preventive care. Although these services are indeed of high priority, the effective provision of comprehensive reproductive health services is often not realized. The provision of these services is even more elusive for the woman with chronic renal disease who often relies on her nephrologist for her primary health care. In one study, only 13% of women on dialysis had had discussions with their nephrologist about menstrual function, contraception, and possible pregnancy.1 Therefore, the nephrologist should be prepared to inquire about and discuss the issues of menstruation, contraception, and family planning. Although most women on dialysis do not ovulate and are amenorrheic, ovarian function in women with ESRD has infrequently been
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The Primary Care of Women With ESRD
Table 2. Immunization Recommendations for Adults
Vaccine
Indicated for
Dosage & Schedule
Contraindications
Booster every 10 years of 0.5 mL 1M after completion of primary series of 3 doses
Neurological or anaphylactic reaction or hypersensitivity to previous dose Pregnancy; immunocompromised patients
Tetanus-diphtheria
All adults
Measles (live vaccine) (should be given as MMR)
1 dose of 0.5 mL SC at least 1 Unimmunized born after 1956 month apart 2 doses of 0.5 rnL sc: High-risk groups, such as health care workers, students entering college, international travelers, or previously immunized with 1 dose Women of childbearing age 1 dose of 0.5 mL SC Pregnancy; immunocomand health care workers promised patients without immunity High risk patients, such as 3 doses of 1 mLIM at 0, I, 6 those on hemodialysis months and health care workers Adults 65 years or older; 0.5 mL 1M annually Egg allergy patients with medical problems including renal dysfunction; persons caring for those at risk 0.5 mL 1M or SC once Adults 65 years or older; patients with chronic illness including chronic renal failure
Rubella (attenuated live virus) (usually given asMMR) Hepatitis B Influenza
Pneumococcal
Abbreviations: MMR, measles, mumps, rubella; 1M, intramuscularly; SC, subcutaneously. Adapted and reprinted with permiSSion from the Immunization Action Coalition (lAC): Summary of Recommendations for Adult Immunization, 1999.
studied. Previously, approximately 10% of premenopausal patients on dialysis were reported to menstruate regularly.2 This picture has changed substantially, however. Although most of the women on dialysis in a recent study reported irregularity of menses, 42% were currently menstruating.! Available studies suggest that the anovulation observed in women on dialysis is likely caused by a hypothalamic defect, such as an inhibition of the estradiol-stimulated LH surge, but the precise pathophysiologic alterations remain unclear.3 In addition, about 70% of women with ESRD have hyperprolactinemia as a result of reduced renal clearance, increased secretion of prolactin by the anterior pituitary, and anterior pituitary resistance to the downregulatory effects of dopamine. 4 Little information exists about the menstrual patterns of women with chronic renal disease since the advent of recombinant human erythropoeitin, which may alter menstrual and ovulatory patterns, improve hyperprolactinemia, and improve sexual interest and function.
The logical question follOWing menstrual history is one of sexual activity and contraception. Compared with normal, healthy women, fewer women on dialysis, regardless of age, are sexually active. 1 Physiologic factors, such as hyperprolactinemia, metabolic and vascular changes, anemia, and the use of antihypertensive medications, may contribute to this reduced sexual activity in women on dialysis. In addition, the influence of psychosocial stresses imposed on individuals with chronic illness is formidable and cannot be ignored. Dialysis access and its attendant problems cause changes in body image that may adversely affect the patient's sense of sexuality. Depression and fatigue are also contributing factors. The lack of studies examining sexual activity and sexuality in women with ESRD limits our understanding of this issue, but those studies that exist have all found reduced sexual activity and satisfaction with sexual relationships after women begin dialysis.1,3,4 These studies also found that communication about sexual status was less than optimal
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between patients and nephrologists. It is important for the renal health care team to inquire about sex, intimacy, and sexual dysfunction. Open discussion about these topics can help the patient feel more comfortable with her sexuality and perhaps lead to treatment modalities to improve this aspect of life. The potential for pregnancy among women with ESRO is influenced by uremia-induced hormonal alterations as well as nonhormonal psychosocial factors. Thus, the likelihood of conception in any given individual will depend on the interplay of these factors in addition to the reluctance of patients with chronic illness to attempt pregnancy. Though uncommon, because conception can occur in uremic women of childbearing age, women on dialysis should be counseled about contraception. The literature contains few references to the safety and efficacy of contraceptive methods in women with ESRO, but there is no reason to believe that this group of women differs from healthy women regarding contraceptive risks. Barrier methods of contraception (diaphragms, condoms, cervical caps) can safely be used in all dialysis patients. Latex condoms have the added benefit of helping to prevent the spread of sexually transmitted diseases. Peritonitis has been associated with the use of an intrauterine device,3 suggesting that this method of contraception is probably not the method of choice for women receiving peritoneal dialysis and women more susceptible to infection, such as diabetic or immunocompromised individuals. Oral contraceptives are an effective method of contraception and may confer additional benefits, such as reducing the risk of osteoporosis and atherosclerosis, in women with ESRO who are estrogen deficient. The limited experience in the literature suggests that oral contraceptives are not associated with an increased incidence of vascular access thrombosis in women on hemodialysis. Metabolism of estrogen may be altered in patients receiving peritoneal dialysis, however, with a decreased clearance of oral estradiol and a significant amount of estrogen lost via the PO fluid dail ys,6; these considerations must be taken into account. In addition, oral hormonal contraception may not be appropriate in women with uncontrolled hypertension, smokers over the age of 35, poorly controlled
diabetics, and women known to be positive for the anticardiolipin (antiphospholipid) antibody. This form of contraception is generally contraindicated in women with a previous history of thromboembolic disease, breast cancer, endometrial cancer, or other estrogendependent neoplasia. Progestin only oral contraceptives may be an alternative for some of these patients. Intramuscular injection of medroxyprogesterone acetate every 3 months and progestin implants are effective methods of contraception but have not been studied specifically in patients with ESRO. Surgical sterilization is an option for women who do not desire future fertility and must be regarded as permanent.
Mid-Life Women's Health Menopause
Menopause is the permanent cessation of menstruation that occurs after the loss of ovarian activity. The neuroendocrine changes that occur, namely the loss of estrogen, may produce numerous adverse effects. Some of these sequelae, such as vasomotor symptoms, urogenital atrophy, loss of skin thickness and elasticity, and sleep disturbances, may affect quality of life. Estrogen deficiency may also affect a woman's risk for certain chronic diseases, chiefly osteoporosis and ischemic heart disease, and therefore affect not only quality of life, but longevity. Menopause occurs at a younger age among women with ESRO. The median age of menopause is 47 years among the population of women with ESRD as compared with 51 to 51.5 years in healthy North American women. Fewer women with ESRD appear to receive hormone replacement therapy than women without chronic renal disease. In one study, only 5% of women on dialysis over the age of 55 were receiving hormone replacement therapy'! Little data exist about the use of hormone replacement therapy specifically in women with ESRO. As in healthy women, when absolute contraindications, such as estrogen-dependent neoplasms, undiagnosed genital bleeding, active liver disease, pregnancy, or active thromboembolic disease or a history of recurrent thromboembolic events, do not exist,
The Primary Care of Women With ESRD
all women should be considered potential candidates for hormone replacement. Epidemiological data have shown that postmenopausal hormone replacement therapy (HRT) reduces all-cause mortality and currently favors the use of HRT to protect against accelerated bone mass loss, reduce the incidence and severity of heart disease, improve psychological function, and generally improve the quality of life. When making a risk/benefit analysis of HRT, the risk of coronary artery disease is felt to be the most important factor, as death from ischemic heart disease is 4 to 5 times more common than death from breast and endometrial cancer combined. There is epidemiological evidence that HRT reduces the risk of coronary artery disease, though almost all of the data comes from observational studies. Perhaps the strongest evidence to date comes from several cross-sectional angiographic studies which examined women who were hospitalized for cardiac catheterization. All of the studies found that women who were on estrogen had half the risk of severely stenotic coronary artery lesions at the time of angiography.? The recent Heart and Estrogen/ Progestin Replacement Study (HERS), the only randomized clinical trial, indicates that estrogen replacement may not be beneficial as secondary prevention (ie, starting HRT after a coronary event)8; however, additional data are needed. The mechanism of estrogen's cardioprotective effect is probably multifold, including direct vasodilatory effects on coronary arteries, effects on endothelial prostacyclin and platelet thromboxane A2, and beneficial alterations in the lipid profile, which may be particularly important in women with ESRD. Prevention of osteoporosis with HRT is well established. Many studies have shown that estrogen prevents bone loss, whereas a steady rate of bone loss is seen in untreated women. In addition, epidemiological studies of HRT indicate a 50% to 80% reduction in vertebral fractures and a 25% reduction in nonvertebral fractures with 5 years of use. The association of HRT with breast cancer remains largely controversial. The data available on breast cancer and HRT have not clearly defined a causal association. Numerous epidemiological studies show varying results; however, the majority show a relative risk no
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greater than 1.3 to 1.5, and most show a relative risk very close to 1 or 1.1. Several meta-analyses suggest that the risk may be related to dose and duration of use and is possibly increased when HRT is given to patients with additional risk factors for breast cancer. 9,lO Issues about HRT and breast cancer (as well as its effects on the heart and bones) may be better clarified by results of the Women's Health Initiative studies now underway. Therapy must be individualized. For this, the patient, her understanding of the benefits and risks, and her participation in the decisions regarding management are instrumental in the approach to menopause. HRT should be discussed with each patient, presenting the perceived benefits in her case and the potential risks or side effects. Physicians providing primary care to women should be well informed about HRT and initiate discussion with their patients. There are currently 3 categories of hormone replacement regimens: unopposed estrogen, cyclic estrogen plus progestin, and continuous estrogen plus progestin. Unopposed estrogen is indicated for women who have undergone hysterectomy, as the indication for adding a progestin is to prevent the increased risk of estrogen-induced endometrial cancer. Cyclic use of combined estrogen and progestin is recommended for most postmenopausal women with an intact uterus. The most popular regimen uses conjugated estrogen 0.625 mg or its equivalent given daily with 5-10 mg of medroxyprogesterone acetate given for 12-14 consecutive days of each month. Eighty-five to 90% of women will have monthly withdrawal bleeding on this regimen. In an effort to avoid menses, a continuous estrogen and progestin regimen can be used. Conjugated estrogen 0.625 mg or its equivalent and 2.5 mg of medroxyprogesterone acetate are given daily. It is important to note that of women using continuous combined regimens, 30% to 50% experience irregular bleeding that can last up to the sixth month of therapy. Most women on this regimen eventually do have amenorrhea. Irregular bleeding after the sixth month of continuous therapy should be regarded as dysfunctional and warrants further investigation.
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Osteoporosis Osteoporosis is the most common bone disease in women. Osteoporosis is defined as a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, leading to an increase in bone fragility and susceptibility to fracture.1 1 The metabolic derangements, such as overproduction of parathyroid hormone, disordered vitamin 0 metabolism, chronic metabolic acidosis, excessive fecal losses of calcium, and skeletal abnormalities that result from ESRD complicate this risk for low bone mass and subsequent fracture. Therefore, prevention, risk assessment, early diagnosis, and prompt treatment of osteoporosis are essential in women with ESRD. The primary care physician should counsel all women on the risk factors for osteoporosis. The factors associated with an increased risk of osteoporotic fracture can be classified as unmodifiable or modifiable. In general, the more risk factors a woman has, the greater her risk of bone density loss and fracture. In addition to the risk factors listed in Table 3, Table 3. Risk Factors for Osteoporotic Fracture
Unmodifiable
Modifiable
Personal history Cigarette of fracture as smoking an adult Low calcium Family history intake
Caucasian/ Asian race
Thin,smail frame
Advanced age
Sedentary lifestyle Alcohol abuse
Treatable Estrogen deficiency Comorbid conditions, including vitaminD deficiency, thyrotoxicosis, hyperparathyroidism Impaired eyesight Recurrent falls
Use of certain pharmacological agents, including corticosteroids, excessive thyroxine, heparin
Data from National Osteoporosis Foundation: Physician's Guide to Prevention and Treatment of Osteoporosis. Belle Meade, NJ, Exerpta Medica, Inc, 1999, pp 1-25. 11
there are a host of diseases and drugs that can be causes of secondary osteoporosis. Of particular interest to the physician caring for the woman with ESRD are gonadal insufficiency, insulin-dependent diabetes mellitus, and hyperparathyroidism. The decision to evaluate bone mineral density should be based on an individual patient's risk profile and whether or not the results will influence treatment decisions. The National Osteoporosis Foundation recommends that bone mineral density testing be performed on all postmenopausal women under age 65 who have 1 or more risk factors for osteoporosis (in addition to menopause); all women age 65 and older regardless of additional risk factors; postmenopausal women who present with fractures; women who are considering therapy for osteoporosis (if bone mineral density testing would facilitate the decision); and women who have been on HRT for prolonged periods because some women will continue to lose bone density despite hormone therapy.ll Evaluation of bone mineral density is usually performed using dual-energy radiograph absorptiometry (DEXA). Universal prevention and treatment strategies for all patients include adequate intake of calcium (1200 mg/ day) and vitamin 0 (400800 IV/day), regular weight bearing exercise, avoidance of tobacco use and alcohol abuse, and minimization of fall risk. Women with chronic renal disease should be evaluated for vitamin D deficiency and may need to be supplemented. Pharmacological options for osteoporosis prevention and/ or treatment are HRT (prevention and treatment), raloxifene (prevention and treatment), and calcitonin (treatment). Alendronate, a bisphosphonate which is approved for both the prevention and treatment of osteoporosis, is currently not recommended for patients with a creatinine clearance less than 35 mL/min.
Special Considerations Endometrial cancer is the most common genital cancer in women age 45 years and older. Oligomenorrhea is common in women with ESRD as discussed previously, and endometrial hyperplasia that can result from oligomenorrhea is a risk factor for the development of
The Primary Care of Women With ESRD
endometrial carcinoma. An increased incidence of endometrial cancer in women dialysis patients compared with nonuremic controls has been identified. 4 This cancer risk appears to be greatest among women 40 years and older who have been amenorrheic for 1 year before a bleeding episode. Though routine screening of asymptomatic women for endometrial cancer and its precursors is not cost-effective, perimenopausal and postmenopausal women with a history or evidence of abnormal uterine bleeding should be evaluated. Evaluation includes a thorough history and pelvic examination and may include a transvaginal ultrasound to examine endometrial thickness and/ or an endometrial biopsy. Vaginal candidiasis, caused most often by the fungus Candida albicans, is a common problem in the normal female population. In women receiving peritoneal dialysis, however, vaginal candidiasis could be a source of fungal peritonitisJ2 Factors which may predispose to candidal overgrowth in women with ESRD include high blood glucose levels; use of antibiotics, especially broad spectrum; use of corticosteroids, especially in high doses; depressed cell-mediated immunity; and possibly, high carbohydrate diets. Patients as well as medical staff should be educated to recognize the symptoms and signs of vulvovaginal candidiasis. Such clinical manifestations include vulvar pruritis, erythema, and burning; vaginal soreness and irritation; thick, white discharge; and external dysuria. Diagnosis may be confirmed by a wet mount of vaginal secretions with 10% KOH preparation that shows mycelia or pseudohyphae or by a routine culture. Prompt treatment is important to avoid possible subsequent fungal peritonitis.
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References 1. Holley JL, Schmidt RJ, Bender FH, et al: Gynecologic and reproductive issues in women on dialysis. Am J Kidney Dis 29:685-690, 1997 2. Lim VS: Reproductive function in patients with renal insufficiency. Am J Kidney Dis 9:363-367, 1987 3. Schmidt RJ, Holley JL: Fertility and contraception in end-stage renal disease. Adv Ren Replace Ther 5:3844,1998 4. Gipson D, Katz LA, Stehman-Breen C: Principles of dialysis: Special issues in women. Semin Nephrol 19:140-147,1999 5. Price T, Dupuis R, Carr B, et al: Single and multiple dose pharmacokinetics of a low dose oral contraceptive in women with chronic renal failure undergoing peritoneal dialysis. Am J Obstet Gynecol 168:14001406,1993 6. Nather S, Nagel S, Deuber H, et al: Sexual hormone concentration in serum and dialysate of CAPD Patients. J Am Soc NephroI8:269A, 1997 7. Martin KA: Menopause and estrogen replacement therapy, in Carlson KJ, Eisenstat SA (eds): Primary Care of Women. St Louis, MO, Mosby, 1995, pp 251-256 8. Hulley S, Grady D, Bush T, et al: Randomized trail of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/Progestin Replacement Study (HERS) Research Group. JAMA 280:605-613,1998 9. DuPont WD, Page DL: Menopausal estrogen replacement therapy and breast cancer. Arch Intern Med 151:67-72,1991 10. Steinberg KK, Thacker SB, Smith SJ, et al: A metaanalysis of the effect of estrogen replacement therapy on the risk of breast cancer. JAMA 265:1985-1990,1991 11. National Osteoporosis Foundation: Physician's Guide to Prevention and Treatment of Osteoporosis. Belle Meade, NJ, Exerpta Medica, Inc, 1999, pp 1-25 12. Castillo AA, Lew SQ, Smith AM, et al: Vaginal candidiasis: A potential source of fungal peritonitis in peritoneal dialysis. Perit Dial Int 18:338-339, 1998 13. U.S. Preventive Services Task Force: Guide to Clinical Preventive Services (ed 2). Baltimore, MD, Williams & Wilkins, 1996 14. Adult Influenza and Pneumococcal Immunizations: A Postgraduate Medicine Special Report. Mineappolis, MN, McGraw-Hill Companies, Inc, 1999
he population of women with chronic renal disease, including patients with endstage renal disease (ESRD) on peritoneal dialysis and hemodialysis, grows each year. Nephrologists provide most of the medical care to this patient population. Although nephrologists generally address medical issues related to renal disease and the comorbid conditions which frequently exist, attention must be given to preventive care and routine health care maintenance. The need for preventive care in women with ESRD is no less than that for the female population at large. Nephrologists must be prepared to address issues concerning screening for cancer, menstruation, birth control methods, childbearing, and menopause.
T
Prevention and Screening One of the main roles of the primary care physician is to help women stay healthy. If disease does occur, it must be diagnosed as early as possible so as to afford the greatest likelihood of cure or long-term control of the problem, thereby reducing the risk of significant secondary morbidity. The screening and
From the Departments of Medicine and Obstetrics/ Gynecology, Georgetown University Medical Center, Washington, DC. Address correspondence to Andrea J. Singer, MD, Georgetown University Medical Center, Departments of Medicine and Obstetrics/Gynecology, 3 PHC, 3800 Reservoir Road, NW, Washington, DC 20007; e-mail: singeraj@gusun. georgetown.edu. © 2000 by the National Kidney Foundation, Inc. 1073-4449/00/0703-0003$3.00/0 doi:10.1053/jarr.2000.8127
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prevention strategies most important for any given woman will depend on her individual risk profile. The strategies will also change as the woman ages, and they will evolve through the phases of her life. With a few exceptions, screening recommendations for the woman with ESRD are no different than those for the average woman. This section will cover a series of strategies that can be used in practice to optimize the patient's well-being. Routine Assessments Periodic health assessments provide an excellent opportunity to counsel patients about preventive care. These assessments, annually or in an ongoing manner with the ESRD patient, should include screening, evaluation, and counseling based on age and risk factors (Table 1). Personal behavioral characteristics are important aspects of a woman's health. Cigarette smoking contributes substantially to morbidity and mortality. Therefore, the primary care of women should include a routine assessment of smoking status, strong and repeated advice to all smokers to quit, and assistance for those smokers who are ready to stop. Alcohol and drug use are also serious and common problems for women in the United States, and physicians can play a role in decreasing women's risk. All physicians, but especially those providing primary care, must be alert to signs of substance use and abuse, must ask direct questions, and must be willing and able to counsel their patients or refer them for help when necessary. Using the standard weight/height charts or
Advances in Renal Replacement Therapy, Vol 7, No 3 (July), 2000: pp 202-209
The Primary Care of Women With ESRD
Table 1. Preventive Health Services in Adults
Preventive Service Counseling Tobacco/ alcohol! drugs Nutrition Exercise Sexual practices SeU-breastexarnination Sun exposure Injury prevention (seatbelts/hehnets/
Frequency Annually Annually Annually Annually Annually Annually Annually
guns)
Physical examination Blood pressure Weight Height Clinical breast examination Laboratory tests and procedures Cholesterol Pap smear
Manunography Stool for occult blood Flexible sigmoidoscopy
Minimum of every 2 years Each visit or annually Annually Annually after age 40
Every 5 years Begin at age 18 or at the onset of sexual activity; annually for 3 years; if normal, screening interval can be extended to every 2 to 3 years at discretion of physician and patient Every 1 to 2 years from age 40-49; annually after age 50 Annually after age 50 Every 3 to 5 years after age 50
Adapted and reprinted from u.s. Preventive Services Task Force: Guide to Clinical Preventive Services (ed 2). Baltimore, MD, Williams & Wilkins, 1996.13
calculations of body-mass index, by middle age, approximately 35% of white women and 60% of black women are overweight or obese. Proper dietary and exercise habits can substantially reduce the risk of obesity and the illnesses and disabilities associated with it. Decreasing the number of calories from fat, increasing fiber content, maintaining dietary balance in the context of an appropriate renal diet, and identifying a fitness program that will fit a woman's lifestyle and in which she will participate regularly are all important issues for the primary care physician and patient to discuss.
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Just as weight and blood pressure are followed closely in the patient with chronic renal disease, height should be followed as well. It should be measured on initial examination, and thereafter, on a yearly basis. Decreases in height of more than one-half inch should raise concern and alert the physician to the possibility of bone density loss and/or osteoporotic vertebral fractures. Cancer Screening Breast cancer is the most common cancer in women in the United States. Mammography may be used as a screening device or as an adjunct in the diagnosis of a palpable breast mass. At the present time, mammography is the only screening method widely available to detect subclinical or occult breast cancer. Largescale, prospective, controlled studies of screening for breast cancer show that mammography reduces the breast cancer mortality rate for women over 50 years of age. The data for screening mammography in women less than 50 years of age is equivocal and currently limited. Therefore, it is recommended that mammography be offered every 1 to 2 years in women age 40-49 and annually to women over age 50. In addition to mammography, clinical breast examination should be performed annually. For high-risk women (such as those with a family history of premenopausal breast cancer in a first-degree relative or genetic susceptibility documented by the presence of BRCA-l or BRCA-2), screening should begin earlier. Women should be screened for cervical cancer and its precursors. Routine Pap smear screening will decrease the incidence and mortality rates of cervical cancer. The current recommendations for when to perform this test generally adhere to guidelines established by the American College of Obstetricians and Gynecologists and the United States Preventive Health Task Force. Routine Pap tests are recommended annually for women age 18 to 65 until 3 consecutive normal results are obtained, and thereafter at the discretion of the physician and patient. Whether it is cost effective to extend screening beyond age 65 is not entirely apparent. Because many patients in the over-65 age group have not been screened or have not been screened regularly, it seems prudent to allow the physician to make recom-
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mendations for the individual in this age group. Colon cancer causes more deaths among women than all gynecologic malignancies combined. In most cases it is preceded by an adenomatous polyp or polyps. Both polyps and early colonic cancer can be detected by routine screening. The digital rectal examination has limited usefulness because less than 10% of colorectal cancers are within reach of the examiner's finger; however, it can easily be performed at the time of pelvic examination in women. Testing of stool for occult blood is limited in sensitivity and specificity, but it can aid in early detection. Although controversy as to the efficacy of screening in the general population and the best methods for screening exists, the American Cancer Society recommends digital rectal examination beginning at age 40, testing of stool for occult blood annually beginning at age 50, and sigmoidoscopy every 3 to 5 years beginning at age 50. The American College of Physicians supports the American Cancer Society in regard to stool for occult blood and sigmoidoscopy. More comprehensive assessments, such as colonoscopy or double air contrast barium enema, should be undertaken if warranted by other risk factors. The skin is the largest human organ and has the highest exposure to direct carcinogens, particularly sunlight. It is not surprising, then, that squamous cell and basal cell carcinomas are 2 of the most common forms of cancer. Though squamous and basal cell cancers are not usually associated with major disability or death, malignant melanoma is associated with increased mortality if not diagnosed early. During history taking, the physician should inquire as to whether a new skin growth has appeared or an existing one has changed color or become symptomatic. An annual complete skin examination should be performed with special attention given to sun-exposed parts of the body. Patients in high-risk groups, such as those with increased recreational or occupational exposure to sunlight, may be referred to a dermatologist. Instruction in skin selfexamination, including vulvar skin, should be a routine part of wellness care. Recommendations for the use of protective clothing, hats, and sunscreen with a sun protective factor (SPF) of 15 or greater should be made as well.
Immunizations General recommendations on immunization in the United States are those of the Immunization Practices Advisory Committee of the Center for Disease Control. Six vaccines are recommended for routine use in adults living in the United States. These include tetanus-diphtheria, measles, rubella, influenza, hepatitis B, and pneumococcus (Table 2). Several points should be highlighted with respect to immunizations in women with chronic renal disease. Influenza vaccines are recommended annually, regardless of age, for all people with renal dysfunction. Pneumococcal vaccine is similarly recommended, regardless of age, for patients with chronic renal failure. Though generally given as a 1-time dose, pneumococcal revaccination is recommended 5 years after the initial vaccination for people at the highest risk of fatal pneumococcal infection or rapid antibody loss, such as those patients with chronic renal disease. The hepatitis B vaccine series should be administered to patients in hemodialysis units and patients with renal disease that may result in dialysis. For dosing regimens, please refer to Table 2.
Reproductive Health Reproductive health encompasses a broad range of services for women of reproductive age, including contraception; sexually transmitted disease and HIV prevention; prenatal, intrapartum, and postpartum care; and counseling regarding healthy lifestyles and the benefits of preventive care. Although these services are indeed of high priority, the effective provision of comprehensive reproductive health services is often not realized. The provision of these services is even more elusive for the woman with chronic renal disease who often relies on her nephrologist for her primary health care. In one study, only 13% of women on dialysis had had discussions with their nephrologist about menstrual function, contraception, and possible pregnancy.1 Therefore, the nephrologist should be prepared to inquire about and discuss the issues of menstruation, contraception, and family planning. Although most women on dialysis do not ovulate and are amenorrheic, ovarian function in women with ESRD has infrequently been
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The Primary Care of Women With ESRD
Table 2. Immunization Recommendations for Adults
Vaccine
Indicated for
Dosage & Schedule
Contraindications
Booster every 10 years of 0.5 mL 1M after completion of primary series of 3 doses
Neurological or anaphylactic reaction or hypersensitivity to previous dose Pregnancy; immunocompromised patients
Tetanus-diphtheria
All adults
Measles (live vaccine) (should be given as MMR)
1 dose of 0.5 mL SC at least 1 Unimmunized born after 1956 month apart 2 doses of 0.5 rnL sc: High-risk groups, such as health care workers, students entering college, international travelers, or previously immunized with 1 dose Women of childbearing age 1 dose of 0.5 mL SC Pregnancy; immunocomand health care workers promised patients without immunity High risk patients, such as 3 doses of 1 mLIM at 0, I, 6 those on hemodialysis months and health care workers Adults 65 years or older; 0.5 mL 1M annually Egg allergy patients with medical problems including renal dysfunction; persons caring for those at risk 0.5 mL 1M or SC once Adults 65 years or older; patients with chronic illness including chronic renal failure
Rubella (attenuated live virus) (usually given asMMR) Hepatitis B Influenza
Pneumococcal
Abbreviations: MMR, measles, mumps, rubella; 1M, intramuscularly; SC, subcutaneously. Adapted and reprinted with permiSSion from the Immunization Action Coalition (lAC): Summary of Recommendations for Adult Immunization, 1999.
studied. Previously, approximately 10% of premenopausal patients on dialysis were reported to menstruate regularly.2 This picture has changed substantially, however. Although most of the women on dialysis in a recent study reported irregularity of menses, 42% were currently menstruating.! Available studies suggest that the anovulation observed in women on dialysis is likely caused by a hypothalamic defect, such as an inhibition of the estradiol-stimulated LH surge, but the precise pathophysiologic alterations remain unclear.3 In addition, about 70% of women with ESRD have hyperprolactinemia as a result of reduced renal clearance, increased secretion of prolactin by the anterior pituitary, and anterior pituitary resistance to the downregulatory effects of dopamine. 4 Little information exists about the menstrual patterns of women with chronic renal disease since the advent of recombinant human erythropoeitin, which may alter menstrual and ovulatory patterns, improve hyperprolactinemia, and improve sexual interest and function.
The logical question follOWing menstrual history is one of sexual activity and contraception. Compared with normal, healthy women, fewer women on dialysis, regardless of age, are sexually active. 1 Physiologic factors, such as hyperprolactinemia, metabolic and vascular changes, anemia, and the use of antihypertensive medications, may contribute to this reduced sexual activity in women on dialysis. In addition, the influence of psychosocial stresses imposed on individuals with chronic illness is formidable and cannot be ignored. Dialysis access and its attendant problems cause changes in body image that may adversely affect the patient's sense of sexuality. Depression and fatigue are also contributing factors. The lack of studies examining sexual activity and sexuality in women with ESRD limits our understanding of this issue, but those studies that exist have all found reduced sexual activity and satisfaction with sexual relationships after women begin dialysis.1,3,4 These studies also found that communication about sexual status was less than optimal
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between patients and nephrologists. It is important for the renal health care team to inquire about sex, intimacy, and sexual dysfunction. Open discussion about these topics can help the patient feel more comfortable with her sexuality and perhaps lead to treatment modalities to improve this aspect of life. The potential for pregnancy among women with ESRO is influenced by uremia-induced hormonal alterations as well as nonhormonal psychosocial factors. Thus, the likelihood of conception in any given individual will depend on the interplay of these factors in addition to the reluctance of patients with chronic illness to attempt pregnancy. Though uncommon, because conception can occur in uremic women of childbearing age, women on dialysis should be counseled about contraception. The literature contains few references to the safety and efficacy of contraceptive methods in women with ESRO, but there is no reason to believe that this group of women differs from healthy women regarding contraceptive risks. Barrier methods of contraception (diaphragms, condoms, cervical caps) can safely be used in all dialysis patients. Latex condoms have the added benefit of helping to prevent the spread of sexually transmitted diseases. Peritonitis has been associated with the use of an intrauterine device,3 suggesting that this method of contraception is probably not the method of choice for women receiving peritoneal dialysis and women more susceptible to infection, such as diabetic or immunocompromised individuals. Oral contraceptives are an effective method of contraception and may confer additional benefits, such as reducing the risk of osteoporosis and atherosclerosis, in women with ESRO who are estrogen deficient. The limited experience in the literature suggests that oral contraceptives are not associated with an increased incidence of vascular access thrombosis in women on hemodialysis. Metabolism of estrogen may be altered in patients receiving peritoneal dialysis, however, with a decreased clearance of oral estradiol and a significant amount of estrogen lost via the PO fluid dail ys,6; these considerations must be taken into account. In addition, oral hormonal contraception may not be appropriate in women with uncontrolled hypertension, smokers over the age of 35, poorly controlled
diabetics, and women known to be positive for the anticardiolipin (antiphospholipid) antibody. This form of contraception is generally contraindicated in women with a previous history of thromboembolic disease, breast cancer, endometrial cancer, or other estrogendependent neoplasia. Progestin only oral contraceptives may be an alternative for some of these patients. Intramuscular injection of medroxyprogesterone acetate every 3 months and progestin implants are effective methods of contraception but have not been studied specifically in patients with ESRO. Surgical sterilization is an option for women who do not desire future fertility and must be regarded as permanent.
Mid-Life Women's Health Menopause
Menopause is the permanent cessation of menstruation that occurs after the loss of ovarian activity. The neuroendocrine changes that occur, namely the loss of estrogen, may produce numerous adverse effects. Some of these sequelae, such as vasomotor symptoms, urogenital atrophy, loss of skin thickness and elasticity, and sleep disturbances, may affect quality of life. Estrogen deficiency may also affect a woman's risk for certain chronic diseases, chiefly osteoporosis and ischemic heart disease, and therefore affect not only quality of life, but longevity. Menopause occurs at a younger age among women with ESRO. The median age of menopause is 47 years among the population of women with ESRD as compared with 51 to 51.5 years in healthy North American women. Fewer women with ESRD appear to receive hormone replacement therapy than women without chronic renal disease. In one study, only 5% of women on dialysis over the age of 55 were receiving hormone replacement therapy'! Little data exist about the use of hormone replacement therapy specifically in women with ESRO. As in healthy women, when absolute contraindications, such as estrogen-dependent neoplasms, undiagnosed genital bleeding, active liver disease, pregnancy, or active thromboembolic disease or a history of recurrent thromboembolic events, do not exist,
The Primary Care of Women With ESRD
all women should be considered potential candidates for hormone replacement. Epidemiological data have shown that postmenopausal hormone replacement therapy (HRT) reduces all-cause mortality and currently favors the use of HRT to protect against accelerated bone mass loss, reduce the incidence and severity of heart disease, improve psychological function, and generally improve the quality of life. When making a risk/benefit analysis of HRT, the risk of coronary artery disease is felt to be the most important factor, as death from ischemic heart disease is 4 to 5 times more common than death from breast and endometrial cancer combined. There is epidemiological evidence that HRT reduces the risk of coronary artery disease, though almost all of the data comes from observational studies. Perhaps the strongest evidence to date comes from several cross-sectional angiographic studies which examined women who were hospitalized for cardiac catheterization. All of the studies found that women who were on estrogen had half the risk of severely stenotic coronary artery lesions at the time of angiography.? The recent Heart and Estrogen/ Progestin Replacement Study (HERS), the only randomized clinical trial, indicates that estrogen replacement may not be beneficial as secondary prevention (ie, starting HRT after a coronary event)8; however, additional data are needed. The mechanism of estrogen's cardioprotective effect is probably multifold, including direct vasodilatory effects on coronary arteries, effects on endothelial prostacyclin and platelet thromboxane A2, and beneficial alterations in the lipid profile, which may be particularly important in women with ESRD. Prevention of osteoporosis with HRT is well established. Many studies have shown that estrogen prevents bone loss, whereas a steady rate of bone loss is seen in untreated women. In addition, epidemiological studies of HRT indicate a 50% to 80% reduction in vertebral fractures and a 25% reduction in nonvertebral fractures with 5 years of use. The association of HRT with breast cancer remains largely controversial. The data available on breast cancer and HRT have not clearly defined a causal association. Numerous epidemiological studies show varying results; however, the majority show a relative risk no
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greater than 1.3 to 1.5, and most show a relative risk very close to 1 or 1.1. Several meta-analyses suggest that the risk may be related to dose and duration of use and is possibly increased when HRT is given to patients with additional risk factors for breast cancer. 9,lO Issues about HRT and breast cancer (as well as its effects on the heart and bones) may be better clarified by results of the Women's Health Initiative studies now underway. Therapy must be individualized. For this, the patient, her understanding of the benefits and risks, and her participation in the decisions regarding management are instrumental in the approach to menopause. HRT should be discussed with each patient, presenting the perceived benefits in her case and the potential risks or side effects. Physicians providing primary care to women should be well informed about HRT and initiate discussion with their patients. There are currently 3 categories of hormone replacement regimens: unopposed estrogen, cyclic estrogen plus progestin, and continuous estrogen plus progestin. Unopposed estrogen is indicated for women who have undergone hysterectomy, as the indication for adding a progestin is to prevent the increased risk of estrogen-induced endometrial cancer. Cyclic use of combined estrogen and progestin is recommended for most postmenopausal women with an intact uterus. The most popular regimen uses conjugated estrogen 0.625 mg or its equivalent given daily with 5-10 mg of medroxyprogesterone acetate given for 12-14 consecutive days of each month. Eighty-five to 90% of women will have monthly withdrawal bleeding on this regimen. In an effort to avoid menses, a continuous estrogen and progestin regimen can be used. Conjugated estrogen 0.625 mg or its equivalent and 2.5 mg of medroxyprogesterone acetate are given daily. It is important to note that of women using continuous combined regimens, 30% to 50% experience irregular bleeding that can last up to the sixth month of therapy. Most women on this regimen eventually do have amenorrhea. Irregular bleeding after the sixth month of continuous therapy should be regarded as dysfunctional and warrants further investigation.
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Osteoporosis Osteoporosis is the most common bone disease in women. Osteoporosis is defined as a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, leading to an increase in bone fragility and susceptibility to fracture.1 1 The metabolic derangements, such as overproduction of parathyroid hormone, disordered vitamin 0 metabolism, chronic metabolic acidosis, excessive fecal losses of calcium, and skeletal abnormalities that result from ESRD complicate this risk for low bone mass and subsequent fracture. Therefore, prevention, risk assessment, early diagnosis, and prompt treatment of osteoporosis are essential in women with ESRD. The primary care physician should counsel all women on the risk factors for osteoporosis. The factors associated with an increased risk of osteoporotic fracture can be classified as unmodifiable or modifiable. In general, the more risk factors a woman has, the greater her risk of bone density loss and fracture. In addition to the risk factors listed in Table 3, Table 3. Risk Factors for Osteoporotic Fracture
Unmodifiable
Modifiable
Personal history Cigarette of fracture as smoking an adult Low calcium Family history intake
Caucasian/ Asian race
Thin,smail frame
Advanced age
Sedentary lifestyle Alcohol abuse
Treatable Estrogen deficiency Comorbid conditions, including vitaminD deficiency, thyrotoxicosis, hyperparathyroidism Impaired eyesight Recurrent falls
Use of certain pharmacological agents, including corticosteroids, excessive thyroxine, heparin
Data from National Osteoporosis Foundation: Physician's Guide to Prevention and Treatment of Osteoporosis. Belle Meade, NJ, Exerpta Medica, Inc, 1999, pp 1-25. 11
there are a host of diseases and drugs that can be causes of secondary osteoporosis. Of particular interest to the physician caring for the woman with ESRD are gonadal insufficiency, insulin-dependent diabetes mellitus, and hyperparathyroidism. The decision to evaluate bone mineral density should be based on an individual patient's risk profile and whether or not the results will influence treatment decisions. The National Osteoporosis Foundation recommends that bone mineral density testing be performed on all postmenopausal women under age 65 who have 1 or more risk factors for osteoporosis (in addition to menopause); all women age 65 and older regardless of additional risk factors; postmenopausal women who present with fractures; women who are considering therapy for osteoporosis (if bone mineral density testing would facilitate the decision); and women who have been on HRT for prolonged periods because some women will continue to lose bone density despite hormone therapy.ll Evaluation of bone mineral density is usually performed using dual-energy radiograph absorptiometry (DEXA). Universal prevention and treatment strategies for all patients include adequate intake of calcium (1200 mg/ day) and vitamin 0 (400800 IV/day), regular weight bearing exercise, avoidance of tobacco use and alcohol abuse, and minimization of fall risk. Women with chronic renal disease should be evaluated for vitamin D deficiency and may need to be supplemented. Pharmacological options for osteoporosis prevention and/ or treatment are HRT (prevention and treatment), raloxifene (prevention and treatment), and calcitonin (treatment). Alendronate, a bisphosphonate which is approved for both the prevention and treatment of osteoporosis, is currently not recommended for patients with a creatinine clearance less than 35 mL/min.
Special Considerations Endometrial cancer is the most common genital cancer in women age 45 years and older. Oligomenorrhea is common in women with ESRD as discussed previously, and endometrial hyperplasia that can result from oligomenorrhea is a risk factor for the development of
The Primary Care of Women With ESRD
endometrial carcinoma. An increased incidence of endometrial cancer in women dialysis patients compared with nonuremic controls has been identified. 4 This cancer risk appears to be greatest among women 40 years and older who have been amenorrheic for 1 year before a bleeding episode. Though routine screening of asymptomatic women for endometrial cancer and its precursors is not cost-effective, perimenopausal and postmenopausal women with a history or evidence of abnormal uterine bleeding should be evaluated. Evaluation includes a thorough history and pelvic examination and may include a transvaginal ultrasound to examine endometrial thickness and/ or an endometrial biopsy. Vaginal candidiasis, caused most often by the fungus Candida albicans, is a common problem in the normal female population. In women receiving peritoneal dialysis, however, vaginal candidiasis could be a source of fungal peritonitisJ2 Factors which may predispose to candidal overgrowth in women with ESRD include high blood glucose levels; use of antibiotics, especially broad spectrum; use of corticosteroids, especially in high doses; depressed cell-mediated immunity; and possibly, high carbohydrate diets. Patients as well as medical staff should be educated to recognize the symptoms and signs of vulvovaginal candidiasis. Such clinical manifestations include vulvar pruritis, erythema, and burning; vaginal soreness and irritation; thick, white discharge; and external dysuria. Diagnosis may be confirmed by a wet mount of vaginal secretions with 10% KOH preparation that shows mycelia or pseudohyphae or by a routine culture. Prompt treatment is important to avoid possible subsequent fungal peritonitis.
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References 1. Holley JL, Schmidt RJ, Bender FH, et al: Gynecologic and reproductive issues in women on dialysis. Am J Kidney Dis 29:685-690, 1997 2. Lim VS: Reproductive function in patients with renal insufficiency. Am J Kidney Dis 9:363-367, 1987 3. Schmidt RJ, Holley JL: Fertility and contraception in end-stage renal disease. Adv Ren Replace Ther 5:3844,1998 4. Gipson D, Katz LA, Stehman-Breen C: Principles of dialysis: Special issues in women. Semin Nephrol 19:140-147,1999 5. Price T, Dupuis R, Carr B, et al: Single and multiple dose pharmacokinetics of a low dose oral contraceptive in women with chronic renal failure undergoing peritoneal dialysis. Am J Obstet Gynecol 168:14001406,1993 6. Nather S, Nagel S, Deuber H, et al: Sexual hormone concentration in serum and dialysate of CAPD Patients. J Am Soc NephroI8:269A, 1997 7. Martin KA: Menopause and estrogen replacement therapy, in Carlson KJ, Eisenstat SA (eds): Primary Care of Women. St Louis, MO, Mosby, 1995, pp 251-256 8. Hulley S, Grady D, Bush T, et al: Randomized trail of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/Progestin Replacement Study (HERS) Research Group. JAMA 280:605-613,1998 9. DuPont WD, Page DL: Menopausal estrogen replacement therapy and breast cancer. Arch Intern Med 151:67-72,1991 10. Steinberg KK, Thacker SB, Smith SJ, et al: A metaanalysis of the effect of estrogen replacement therapy on the risk of breast cancer. JAMA 265:1985-1990,1991 11. National Osteoporosis Foundation: Physician's Guide to Prevention and Treatment of Osteoporosis. Belle Meade, NJ, Exerpta Medica, Inc, 1999, pp 1-25 12. Castillo AA, Lew SQ, Smith AM, et al: Vaginal candidiasis: A potential source of fungal peritonitis in peritoneal dialysis. Perit Dial Int 18:338-339, 1998 13. U.S. Preventive Services Task Force: Guide to Clinical Preventive Services (ed 2). Baltimore, MD, Williams & Wilkins, 1996 14. Adult Influenza and Pneumococcal Immunizations: A Postgraduate Medicine Special Report. Mineappolis, MN, McGraw-Hill Companies, Inc, 1999